crossing96/oncoscreening huggingface dataset:
Clinical course of patients with renal cell carcinoma or urothelial carcinoma who had stable disease as an initial response to a PD-1 or PD-L1 inhibitor.	BACKGROUND: About 17%-34% of patients with non-prostatic genitourinary (GU) cancer had stable disease (SD) as their best response to programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. However, most efficacy studies of PD-1/PD-L1 inhibitors are focused on the response and its durability. Little is known about patients' clinical outcomes with SD as their initial response to PD-1/PD-L1 inhibitors. METHODS: We retrospectively reviewed the clinical outcomes of patients with renal cell carcinoma (RCC) (n = 102) and urothelial carcinoma (UC) (n = 101) treated with PD-1/PD-L1 inhibitors. The duration of SD (DoSD) was calculated for patients who had SD as their best response and was defined from the time of SD to radiologically confirmed progressive disease (PD) or death. RESULTS: Fifty-five patients (27.1%) had SD as the initial response. Among them, 10 patients (18.2%) achieved a response on subsequent assessments. With a median follow-up duration of 15.2 months, the median DoSD was 8.5 months (range: 3.2-13.8), which was significantly different according to the disease; 9.4 months in RCC and 2.3 months in UC (p = 0.03). If the disease did not progress in 4 months (long SD subgroup), the DoSD (11.0 months) was comparable to the duration of response (12.9 months) in patients who achieved a complete or partial response to PD-1/PD-L1 inhibitors. In addition to the cancer type, the clinical factors associated with short DoSD were liver metastases (p = 0.003), neutrophil-lymphocyte ratio (NLR) > 4.0 (p = 0.001), and platelet-lymphocyte ratio (PLR) > 194 (p = 0.003). CONCLUSION: For RCC patients with SD to PD-1/PD-L1 inhibitors, if there are no liver metastases and NLR/PLR is below the certain level, they would have similar duration of disease control and survival benefit as those who achieve the response.	bladder
Metastasis-directed radiation therapy after radical cystectomy for bladder cancer.	PURPOSE: Metastasis-directed radiation therapy (MDRT) may improve oncologic and quality of life outcomes in patients with metastatic cancer, but data on its use in metastatic bladder cancer is severely limited. We sought to review our institutional experience with MDRT in patients with metastatic bladder cancer following radical cystectomy. MATERIALS AND METHODS: We reviewed records of patients who underwent radical cystectomy and subsequent MDRT at our institution between 2009 and 2020. Baseline demographic and clinical/pathologic factors were collected, as were details of treatment including systemic therapy and MDRT. Cases were categorized by treatment intent as consolidative (intended to prolong survival) and palliative (intended only to relieve symptoms). Response to treatment, survival, and toxicity outcomes were reviewed. RESULTS: A total of 52 patients underwent MDRT following radical cystectomy. MDRT was categorized as consolidative in 40% of cases and palliative in 60%. Toxicity (CTCAE Grade ≥ 2) was reported in 15% of patients, none of which exceeded Grade 3. Most patients undergoing consolidative MDRT were treated with SBRT techniques (76%) and a majority (67%) received concurrent treatment with an immuno-oncology agent. Among patients treated with consolidative intent, 2-year progression-free and overall survival were 19% and 60%, respectively. CONCLUSION: MDRT is safe and well-tolerated by a majority of patients. A majority of patients treated with consolidative intent survived ≥ 2 years from treatment.	bladder
Risk factors associated with positive surgical margins' location at radical cystectomy and their impact on bladder cancer survival.	PURPOSE: To evaluate the risk factors associated with positive surgical margins' (PSMs) location and their impact on disease-specific survival (DSS) in patients with bladder cancer (BCa) undergoing radical cystectomy (RC). METHODS: We analyzed a large multi-institutional cohort of patients treated with upfront RC for non-metastatic (cT1-4aN0M0) BCa. Multivariable binomial logistic regression analyses were used to assess the risk of PSMs at RC for each location after adjusting for clinicopathological covariates. The Kaplan-Meier method was used to estimate DSS stratified by margins' status and location. Log-rank statistics and Cox' regression models were used to determine significance. RESULTS: A total of 1058 patients were included and 108 (10.2%) patients had PSMs. PSMs were located at soft-tissue, ureter(s), and urethra in 57 (5.4%), 30 (2.8%) and 21 (2.0%) patients, respectively. At multivariable analysis, soft-tissue PSMs were independently associated with pathological stage T4 (pT4) (Odds ratio (OR) 6.20, p  <  0.001) and lymph-node metastases (OR 1.86, p  =  0.04). Concomitant carcinoma-in-situ (CIS) was an independent risk factor for ureteric PSMs (OR 6.31, p  =  0.003). Finally, urethral PSMs were independently correlated with pT4-stage (OR 5.10, p  =  0.01). The estimated 3-years DSS rates were 58.2%, 32.4%, 50.1%, and 40.3% for negative SMs, soft-tissue-, ureteric- and urethral PSMs, respectively (log-rank; p  <  0.001). CONCLUSIONS: PSMs' location represents distinct risk factors' patterns. Concomitant CIS was associated with ureteric PSMs. Urethral and soft-tissue PSM showed worse DSS rates. Our results suggest that clinical decision-making paradigms on adjuvant treatment and surveillance might be adapted based on PSM and their location.	bladder
An unusual presentation of synchronous bladder metastases from an oesophageal adenocarcinoma.	Adenocarcinoma of the bladder is a rare form of malignancy accounting for fewer than 2% of bladder tumours. It is most commonly a result of direct invasion from prostatic, rectal or gynaecological primaries and less commonly presents from distant haematological or lymphatic metastasis. We report a rare case of oesophageal carcinoma metastasising to the bladder. It involves a 71-year-old man with progressive dysphagia and diagnostic computerised tomography findings of thickening in the oesophagus, bladder and common bile duct. Subsequent endoscopic biopsies of the oesophageal and bladder abnormalities showed immunohistochemical features consistent with upper gastrointestinal malignancy. This report aims to add to current clinical evidence of this route of metastasis and also highlight some of the key markers used by pathologists in interpretation of specimens. It also emphasises the essential role of a multidisciplinary approach for the diagnosis of such rare conditions.	bladder
Immunotherapy of High Risk Non-Muscle Invasive Bladder Cancer.	Introduction: Bladder cancer remains a prevalent and often lethal cancer. Fortunately, recent clinical trials using immunotherapeutics demonstrate promise to improve treatment outcomes. Several of these immunotherapies have already established their value in the metastatic space and likely will soon have indications in the non-metastatic space.Areas covered: This review will cover immunotherapies ranging for well-studied BCG administration to more novel medications such as PD-L1/PD-1 inhibitors, CTLA-4 inhibitors, IL-15 super agonists, and immune modulating gene therapies. Specifically, this article will address the mechanisms of actions, clinical evidence supporting their use, and the presence of any FDA regulatory approval for these medications in the treatment of high-risk non-muscle invasive bladder cancer.Expert opinion: With the publication of clinical data supporting the use of immunotherapies, these novel medications are likely to be adopted for treatment of high-grade non-metastatic bladder cancer. While BCG is likely to remain a primary medication for high-grade bladder cancer for the near future, BCG will likely be co-administered with immunomodulatory medications in some patients to enhance the medications effect in the future. Clinical trials are still ongoing and will demonstrate which of these multiple treatment options yield results worthy of a modification in our current treatment paradigm.	bladder
Intra-arterial infusion chemotherapy utilizing cisplatin inhibits bladder cancer by decreasing the ﬁbrocytic myeloid-derived suppressor cells in an m6A-dependent manner.	Intra-arterial infusion chemotherapy (IAIC), using immunomodulatory cisplatin, is a novel treatment for bladder cancer (BC) that allows the delivery of specific drugs to the local malignant lesion. To explore the immunomodulatory effect of cisplatin during IAIC, we detected the proportion of immunosuppressed cells in BC tissue from eight BC patients, with the reduction of myeloid-derived suppressor cells (MDSCs), more specifically ﬁbrocytic-MDSCs (f-MDSCs). Further, we demonstrated that cisplatin inhibits their proliferation and immunosuppressive activity. f-MDSCs promote tumor proliferation and metastasis in the BC immune environment. Then, we analyzed the genetic differences detected in samples before and after chemotherapy and found that granulocyte colony-stimulating factors (G-CSF) decreased after IAIC. Furthermore, G-CSF methylation decreased following treatment with cisplatin. Specifically, treatment with cisplatin decreased the methylase (METTL3) levels in BC cells, which is important for G-CSF production. Collectively, cisplatin decreased the number of f-MDSCs during IAIC, by blocking G-CSF methylation via targeting METTL3.	bladder
What Women Want: Radical Cystectomy and Perioperative Sexual Function Educational Needs.	OBJECTIVE: To assess the extent and adequacy of pre-operative sexual function (SF) counseling in females undergoing radical cystectomy (RC) and develop educational material to improve identified deficits. METHODS: A 10-question survey was electronically delivered to all females who underwent RC at a single institution between 2015 and 2020. 23 of 145 patients responded (15.9%). In addition, women on the Bladder Cancer Advocacy Network (BCAN) patient discussion board were also queried. The primary outcome was the development of a patient educational handout based on patient perception of pre-operative SF counseling and self-reported changes in post-operative SF. RESULTS: 22 women, 84% of whom were sexually active, met the inclusion criteria. More than half (12/22, 54.5%) reported receiving no pre-operative counseling regarding possible SF changes while another 27.3% (6/22) received some counseling but desired more. Most women rated vaginal preservation as moderate to very important (17/22, 77.3%) and nearly all women noted at least one change in SF, most commonly dyspareunia (13/22, 59.1%). Most also desired more information regarding female sexual health. Separately, the BCAN discussion board was queried regarding patient preference for modality of pre-operative counseling. 77.8% (14/18) preferred a discussion with provider and 13/18 (72.2%) also wanted a written handout. CONCLUSIONS: Sexual dysfunction is prevalent following RC in women and many desire more pre-operative counseling, regardless of disease stage or receipt of chemotherapy. These findings supported our development of interventions to improve pre-operative education as well as strategies to address post-operative SF changes, such as dyspareunia.	bladder
The efficacy and reliability of VI-RADS in determining candidates for repeated transurethral resection in patients with high-risk non-muscle invasive bladder cancer.	OBJECTIVE: Our study aims to evaluate the efficiency and reliability of Vesical Imaging Reporting Data System (VI-RADS) in prospectively identifying the patients to undergo RE-TURBT in the management of patients with high-risk non-muscle invasive Bladder Cancer(HR-NMIBC).The secondary objective was to evaluate the performance of the VI-RADS scoring system in differentiating between muscle-invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer(NMIBC) prospectively. METHODS: The study included 330 patients who underwent transurethral resection of bladder tumour(TURBT) for Bladder Cancer (BC) in our clinic. All patients underwent multiparametric-magnetic resonance imaging (Mp-MRI) before the operation and VI-RADS scoring was administered. The cut-off value of VI-RADS was accepted as three and above. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the differentiation between NMIBC and MIBC distinction in all patients. Receiver operating characteristic (ROC) analysis was performed to evaluate the performance of the VI-RADS scoring system. In the second phase of the study, patients with MIBC and low-risk NMIBC (LR-NMBIC) were excluded and 158 patients with HR-NMIBC were included, and their sensitivity, specificity, PPV and NPV values were measured. ROC analysis was performed. RESULTS: In all patients, sensitivity, specificity, PPV and NPV values of the VI-RADS scoring in the differentiation of MIBC and NMIBC were 91.3, 91.8, 81.7 and 96.3 respectively. The AUC value was 0.934 (95%CI: 0.903-0.964). Sensitivity, specificity, PPV and NPV values were found to be 87, 91.8, 74.1, 95.2 in the evaluation specifically made for patients with HR-NMIBC. The AUC value was 0.900 (95% CI:0.843-0.957). Inter-reader agreement was excellent (Ƙ = 0.90, 95% CI:0.71-0.95). CONCLUSIONS: The VI-RADS scoring system is an effective and reliable method in determining the patients who will undergo RE-TURBT and in differentiating MIBC and NMIBC.	bladder
Impact of Preoperative Immunonutrition on Perioperative Outcomes following Cystectomy.	PURPOSE: Radical cystectomy (RC) for the management of muscle-invasive bladder cancer remains a morbid procedure with high rates of perioperative complications. The role of preoperative immunonutritional supplementation (pre-INS) in improving post-RC outcomes is promising and needs further validation. MATERIALS AND METHODS: We performed a retrospective review of 204 patients who underwent RC for bladder cancer at a single institution, comparing patients who received oral L-arginine-based pre-INS, and those who did not. Preoperative features, postoperative complications, and readmission data were collected. Outcomes of interest included development of high-grade (Clavien-Dindo III-V) complications, readmission within 30 days, ileus, total parenteral nutrition (TPN) requirement, postoperative infection, and length of stay (LOS). Categorical and continuous outcomes were assessed using Fisher's exact test and Welch T-test, respectively. Multivariable logistic regression (MLoR) analysis was used to identify predictive factors for our outcomes. RESULTS: Patients who received pre-INS had significantly lower odds of requiring postoperative TPN (17.3% vs 35.6%; Fisher p=0.015, OR=0.38) and developing postoperative infection (25% vs 45%; Fisher p=0.003; OR=0.41) but no significant difference in the rates of other outcomes. On MLoR, when adjusting for age, gender, body mass index, Charlson comorbidity index, undergoing neoadjuvant chemotherapy and operative features, pre-INS was a significant predictor of postoperative infection (Fisher p=0.02; OR=0.35) but not for high-grade complications, readmission, ileus, needing TPN or LOS. CONCLUSIONS: Preoperative immunonutrition with an L-arginine-based supplement is associated with significant reduction in postoperative infection, one of the most common complications of RC.	bladder
PD-L1 Tumor Cell Expression in Upper Tract Urothelial Carcinomas is Associated With Higher Pathologic Stage.	BACKGROUND: Upper tract urothelial carcinomas (UTUCs) are a rare and unique subset of urothelial carcinoma (UC). Patients with UTUC may qualify for treatment with immune checkpoint inhibitors if their tumor cells express programmed death ligand-1 (PD-L1). While several large studies have looked at PD-L1 expression in UC, most have not investigated UTUC as a separate group, and most have not used Food and Drug Administration approved PD-L1 stains and scoring systems. Moreover, comparison between studies of PD-L1 expression is challenging as a wide variety of different PD-L1 antibody clones, testing platforms, and cutoff values have been used in the literature. METHODS: This is a retrospective study of 37 cases of resected UTUC. Representative tissue from each case was compiled into tissue microarrays and immunohistochemical stains for PD-L1 (Dako antibody clones 22C3 and 28-8) were performed. PD-L1 staining was evaluated using several established Food and Drug Administration approved scoring systems: tumor proportion score (TPS), combined positive score, and immune cell score. Associations between PD-L1 expression and clinicopathologic features were investigated. RESULTS: Overall expression of PD-L1 in UTUC was 29.7% when using a TPS cutoff of ≥1%. Total of, 55.6% of cases with higher pathologic stage (pT3 or pT4) were positive for PD-L1, compared with only 5.3% of cases with lower pathologic stage (pTis, pT1, or pT2; P=0.0011). When using a combined positive score cutoff of ≥10, there was no significant association between tumor stage and PD-L1 expression. There was no association between PD-L1 positivity and tumor grade, tumor location, sex, or age. There was 100% concordance between 22C3 and 28-8 in terms of positivity rate. CONCLUSIONS: Our study using approved testing methods shows that PD-L1 expression in UTUC is more often associated with high pathologic stage, which may reflect an immune response evasion mechanism that UC cells acquire later in disease progression. In addition we show that 29.7% of UTUCs are positive for PD-L1 TPS expression, comparable to the 20% to 30% reported in UC literature. Finally, PD-L1 22C3 and 28-8 clones show similar overall patterns of staining in this setting.	bladder
Primary Mucinous Adenocarcinoma of the Urinary Bladder: A Rare Entity.	Adenocarcinoma constitutes around 0.5 to 2% of all neoplastic lesions of the urinary bladder, out of which, the mucinous variant is seen on rare occasions. Intestinal metaplasia resulting from nephrolithiasis, chronic inflammation and hydronephrosis could be the precursor lesion. Bladder exstrophy and remnants of the urachus are considered as other possible risk factors. The tumour prefers patients who are over 50 years. Hematuria, difficult voiding and suprapubic pain are the most common presenting symptoms. The tumour has a very bad prognosis and is poorly responsive to chemo and radiotherapy and hence surgery is the treatment of choice. Hence early diagnosis is of paramount importance. While managing adenocarcinoma of the bladder, it is important to rule out any possibility of a metastatic lesion that could have come from other organs where mucinous adenocarcinoma is more common.	bladder
Trousseau's Syndrome Presenting as Multiple Cerebral Infarctions Caused by Mucin-producing Bladder Micropapillary Urothelial Cancer.	We herein report a 70-year-old man with recurrent multiple cerebral infarctions under warfarin therapy who was finally diagnosed with Trousseau's syndrome resulting from advanced bladder cancer. A histological examination of the mesenteric lymph nodes revealed metastasis of micropapillary urothelial cancer with positive mucin markers CA125 and MUC1. Blood examinations also indicated elevated tumor markers, such as CA19-9 and CA125. To our knowledge, this is the first report of Trousseau's syndrome in a patient with bladder micropapillary urothelial cancer in which mucin involvement was clearly proven by histological and serological examinations.	bladder
Circ_0030586 inhibits cell proliferation and stemness in bladder cancer by inactivating the ERK signaling via miR-665/NR4A3 axis.	Increasing evidence reveals that circular RNAs (circRNAs) serve as oncogenes or tumor suppressors in the development of various tumors including bladder cancer (BCa). In this study, we explored the function and mechanism of circ_0030586 (also named circABCC4, ATP binding cassette subfamily C member 4) in BCa. The expression of circ_0030586 was significantly decreased in BCa tissues and cells, as suggested by RT-qPCR. The circular characteristics of circ_0030586 were verified by agarose gel electrophoresis and RNase R treatment. Colony formation, 5-Ethynyl-2'-deoxyuridine and sphere formation assays revealed that overexpression of circ_0030586 suppressed BCa cell proliferation and stemness in vitro. According to xenograft experiment, circ_0030586 overexpression suppressed tumor growth in vivo. Mechanistically, RNA pulldown and luciferase reporter assays were carried out to explore the interaction between genes. Circ_0030586 served as a competing endogenous RNA (ceRNA) for hsa-miR-665 to upregulate the expression of nuclear receptor subfamily 4 group A member 3 (NR4A3) which is a downstream target gene of miR-665 in BCa. MiR-665 exhibited high expression in BCa tissues and cells while NR4A3 expression was downregulated in BCa. MiR-665 overexpression or NR4A3 silencing reversed the suppressive effect of circ_0030586 overexpression on BCa cell proliferation and stemness. Moreover, western blot analysis revealed that circ_0030586 inactivated the extracellular signal-regulated kinase (ERK) pathway by upregulating NR4A3 expression. In conclusion, circ_0030586 inhibits BCa cell proliferation and stemness by serving as a ceRNA for miR-665 to upregulate NR4A3 expression and thus inactivate the ERK signaling.	bladder
Antimony exposure promotes bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy.	Antimony is one of the heavier pnictogens and is widely found in human food chains, water sources, and as an air pollutant. Recent years have seen steadily increasing concentrations of antimony in the ecological environment; critically, several studies have indicated that antimony might pose a tumorigenic risk factor in several cancers. Therefore, antimony toxicity has attracted increasing research attention, with the molecular mechanisms underlying suspected antimony-mediated tumor transformation of greatest interest. Our results showed that the serum concentration of antimony was higher in bladder tumor patients relative to levels in non-tumor patients. Moreover, that such high antimony serum concentration were closely associated with poorer outcome in bladder tumor patients. Additionally, we demonstrated that the presence of antimony promoted both in vitro and in vivo bladder tumor cell growth. Our results also indicated that low-dose antimony resulted in significantly decreased mitochondrial membrane potential, mitochondrial respiratory enzyme complex I/II/III/IV activity, ATP/ADP ratio, and ATP concentration relative to the control group. These findings suggested that antimony caused mitochondrial damage. Finally, we found that low-dose antimony(0.8uM) inhibited mitophagy by deregulating expression of PINK1, Parkin, and p(ser65)-Parkin, and activation of PINK1-Parkin pathway by CCCP could inhibit antimony-induced tumor cell growth. Collectively, this inhibited the proliferation of bladder tumor cells. Overall, our study suggested that antimony promoted bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy. These findings highlight the therapeutic potential in targeting molecules within this antimony induced-PINK1/Parkin signaling pathway and may offer a new approach for the treatment of bladder cancer.	bladder